DESCRIPTION: (Applicant's Abstract) The profound immunosuppressive effects of morphine become conditioned to the environment in which it is administered. This phenomenon is especially exciting since it indicates that exposure to morphine-associated cues suppresses the immune system, which may adversely affect disease susceptibility and pathogenesis in intravenous opioid users, a population with a high rate of HIV infection. The goal of this proposal is to provide new data for the Principal Investigator's newly established independent research program addressing the mechanisms and in vivo disease relevance of this phenomenon. The Principal Investigator's previous work showed that morphine-induced immunosuppression becomes conditioned to the environmental conditioned stimulus paired with administration of the drug. The Principal Investigator obtained preliminary evidence that opioid receptors are necessary for acquisition of the immunosuppressive conditioned response and that expression of the conditioned response involves endogenous opioids. The proposed experiments will extend this work by assessing dose-effect relationships within this phenomenon and pinpointing the underlying mechanisms involved in the acquisition and expression of the conditioned response. For each experiment, the proliferative response of lymphocytes to mitogens, natural killer cell activity, and interleukin-2 production will be evaluated. An additional measure of immune status will begin to address the disease relevance of this conditioned immunosuppression; the proliferative response of splenocytes to an endotoxin toxic shock syndrome toxin-1, will be measured. The proposed studies will provide necessary new data for the design of studies aimed at understanding the in vivo relevance and underlying cellular and molecular mechanisms of conditioned opioid-induced immunosuppression. Moreover, these studies will further understanding of the implications of morphine associated conditioned immunosuppression for HIV-related illness in intravenous drug users.